?R35 Abstract *REVISED* Tannishtha Reya, Ph.D Grant # 1R35CA197699-01 Over the last few decades our remarkable understanding of the molecular basis of oncogenesis has begun to influence cancer therapy at many levels. In the recent past this has led us away from simply relying on blunt tools like chemotherapy and radiation and towards including and designing more molecularly-targeted therapies. Despite these advances, cancer continues to claim millions of lives worldwide. In some very significant part this extraordinary toll is due to our inability to detect the disease early. Early detection of cancer vastly increases the likelihood of effective and durable responses to therapy, and can make the difference between life and death. Considering the potential impact of effective early detection, research in this area lags markedly behind the development of therapeutics. While the field of cancer research has largely focused on developing new therapeutics, there is a critical need to combine this effort with designing new and sensitive strategies that will allow effective early detection. The work we describe here focuses on bridging this gap and providing a more balanced approach to controlling cancer, by combining molecular strategies for design and development of early detection tools coupled with understanding of control points of the transition from benign hyperproliferative phase to a more malignant phase, allowing development of new therapies that can be used for more effective interventions.